Calculation and Analysis of Key Parameters of Underwater Optical Imaging System.

When photographing objects underwater, it is important to utilize an optical window to isolate the imaging device from the water. The properties of the entire imaging system will change, and the imaging quality will decrease due to the refraction impact of the water and the window. The theoretical calculation method for air imaging is no longer relevant in this context. To analyze the unique rule, this research derives the formulas for key parameters of underwater imaging systems under paraxial circumstances. First, the optical window is modeled, then the formula for the optical window's focal length in the underwater environment is derived, and the change rule for the focal length of various window forms underwater is condensed. For the ideal imaging system using a domed optical window, the equivalent two-optical group model of the imaging system is established, and the formula for calculating the focal length, working distance, and depth of field of the underwater imaging system is derived through paraxial ray tracing. The accuracy of the formula is verified through the comparative analysis of the formula calculation results and the Zemax modeling simulation results. It provides an important theoretical basis for the in-depth study of underwater imaging technology.

Long-term clinical outcomes and health-related quality of life in patients with isolated methylmalonic acidemia after liver transplantation: experience from the largest cohort study in China.

BACKGROUND: Liver transplantation (LT) has been proposed as a viable treatment option for selected methylmalonic acidemia (MMA) patients. However, there are still controversies regarding the therapeutic value of LT for MMA. The systematic assessment of health-related quality of life (HRQoL)-targeted MMA children before and after LT is also undetermined. This study aimed to comprehensively assess the long-term impact of LT on MMA, including multiorgan sequelae and HRQoL in children and families. METHODS: We retrospectively evaluated 15 isolated MMA patients undergoing LT at our institution between June 2013 and March 2022. Pre- and post-transplant data were compared, including metabolic profiles, neurologic consequences, growth parameters, and HRQoL. To further assess the characteristics of the HRQoL outcomes in MMA, we compared the results with those of children with biliary atresia (BA). RESULTS: All patients had early onset MMA, and underwent LT at a mean age of 4.3 years. During 1.3-8.2 years of follow-up, the patient and graft survival rates were 100%. Metabolic stability was achieved in all patients with liberalized dietary protein intake. There was a significant overall improvement in height Z scores (P = 0.0047), and some preexisting neurological complications remained stable or even improved after LT. On the Pediatric Quality of Life Inventory (PedsQL™) generic core scales, the mean total, physical health, and psychosocial health scores improved significantly posttransplant (P < 0.05). In the family impact module, higher mean scores were noted for all subscales post-LT, especially family function and daily activities (P < 0.01). However, the total scores on the generic core scales and transplant module were significantly lower (Cohen's d = 0.57-1.17) when compared with BA recipients. In particular, social and school functioning (Cohen's d = 0.86-1.76), treatment anxiety, and communication (Cohen's d = 0.99-1.81) were far behind, with a large effect size. CONCLUSIONS: This large single-center study of the mainland of China showed an overall favorable impact of LT on isolated MMA in terms of long-term survival, metabolic control, and HRQoL in children and families. The potential for persistent neurocognitive impairment and inherent metabolic fragility requires long-term special care. Video Abstract (MP4 153780 KB).

Impact of immunosuppression level on liver allograft fibrosis after pediatric liver transplantation: a retrospective cohort study.

BACKGROUND: Liver allograft fibrosis (LAF) is prevalent among children with long-term survival after liver transplantation (LT). The authors aimed to identify clinical risk factors, with a focus on the impact of immunosuppression (IS) level in the early post-transplant period on LAF. METHODS: A retrospective study was conducted on pediatric LT recipients with at least 1-year of follow-up. Cox regression models were used to analyze risk factors associated with LAF, and landmark analysis was used to evaluate the impact of IS level on LAF. Longitudinal analysis was also conducted in patients with paired biopsies. RESULTS: A total of 139 patients involving 174 liver biopsies were included. With 2.3 to 5.9 years of follow-up, LAF was detected in 91.4% of patients (7.9% were significant), up to 88.2% of whom showed normal liver function. Episodes of acute rejection, biliary complications, cytomegalovirus infection, and prolonged cold ischemia time were independent risk factors. Besides, the risk of LAF in patients with relatively low IS levels at postoperative 1-3, 3-6, 6-12, and 12-36 months was higher than the counterparts. Especially, in patients with relatively high IS levels (mean tacrolimus trough concentration ≥5.1 ng/ml) during postoperative 12-36 months, the risk of LAF was 67% lower in the short future ( P =0.006). In paired analysis, patients with increased IS levels were more likely to achieve fibrosis-reduction (HR=7.53, P =0.025). CONCLUSIONS: Mild to moderate LAF is common among pediatric LT recipients and can appear early and silently. Maintaining adequate levels of IS during 1-3 years after LT seems crucial to ensure protection against LAF.

The severity of valvular heart disease in euthyroid individuals is associated with thyroid hormone levels but not with TSH levels.

Background: Abnormal thyroid function is a metabolic disorder and can lead to several complications, including cardiovascular diseases. In this study, we aimed to examine the relationship between clinical traits and outcomes and the thyroid hormone level of euthyroid individuals with valvular heart disease (VHD). Method: The thyroid function was evaluated in 526 euthyroid VHD patients and 155 healthy control people. As well as clinical indicators were collected and analyzed. Results: No difference in TSH levels (p>0.05) was recorded; however, fT3, TT3, and TT4 levels were lower in the euthyroid VHD patients than in healthy control(4.3 vs 4.63; 1.37 vs 1.48; 97.7 vs 102.09, respectively, all p<0.05), while the fT4 level was higher (12.91 vs 12.35, p<0.05). Moreover, all showed a continuous trend with the change of NYHA grade which does not consist of the incidence of euthyroid sick syndrome(ESS). Further analysis showed that for every 10-fold increase in BNP, fT4 increases by 83%, fT3 decreases by 30%, and TT3 decreases by 12% after being adjusted for other influencing factors. Meanwhile, adjusted fT4 was correlated with multiple worse clinical indicators, which were influenced by age. Conclusion: Thyroid hormones are widely regulated in VHD patients even with acceptable cardiac function, except for TSH level. And the adjusted fT4 is related to worse clinical indicators and outcomes which are only recorded in patients under 53 years old.

The connotation between perioperative glycemic control approach and sternal wound infection in individuals with diabetes mellitus experiencing cardiac surgery: A meta-analysis.

A meta-analysis investigation to measure the connotation between perioperative glycemic control (GC) approach and sternal wound infection (SWI) in individuals with diabetes mellitus (DM) experiencing cardiac surgery (CS). A comprehensive literature inspection till February 2023 was applied and 2654 interrelated investigations were reviewed. The 12 chosen investigations enclosed 1564 individuals with DM and CS in the chosen investigations' starting point, 790 of them were using strict GC, and 774 were using moderate GC. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the Connotation between the perioperative GC approach and SWI in individuals with DM experiencing CS by the dichotomous and continuous approaches and a fixed or random model. Strict GC had significantly lower SWI (OR, 0.33; 95% CI, -0.22-0.50, P < .001) compared with those with moderate GC in individuals with DM and CS. Strict GC had significantly lower SWI compared with those with moderate GC in individuals with DM and CS. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Prognostic Factors Related to In-hospital Death in Children with Biliary Atresia: Analysis of a Nationwide Inpatient Database.

Background and Aims: Patients with biliary atresia (BA) are prone to hepatic decompensation, which might eventually lead to death. This study aimed to identify the possible risk factors affecting in-hospital death in BA patients in China. Methods: We collected data from the Hospital Quality Monitoring System, a national inpatient database. All patients aged up to 2 years old with a diagnosis of BA were included. The subjects were divided to three groups, including Kasai portoenterostomy (KP), liver transplantation (LT), and no surgery. Logistic regression with Firth's method was performed to identify potential influencing variables associated with in-hospital death. Results: During the year 2013 to 2017, there were 14,038 pediatric admissions with a diagnosis of BA. The proportion of in-hospital death in pediatric BA admissions was 1.08%. Compared with patients under six months, there was a higher risk of in-hospital death for children aged six months to 1 year and 1-2 years old. Clinical signs, including cirrhosis, variceal bleeding, and hepatic encephalopathy, were significantly associated with the risk of in-hospital death. In no surgery group, compared to those in Beijing and Shanghai, BA patients admitted in other districts had a lower risk of in-hospital death (OR=0.39, 95% CI: 0.21, 0.70). However, in the LT group, patients admitted in other districts had a higher risk of in-hospital death (OR=9.13, 95% CI: 3.99, 20.87). Conclusions: In-hospital survival remains unsatisfactory for pediatric BA patients with severe complications. Furthermore, more resources and training for BA treatment, especially LT, are essential for districts with poor medical care in the future.

Dendritic cells originating exosomal miR-193b-3p induces regulatory T cells to alleviate liver transplant rejection.

BACKGROUND: Exosomes exert considerable influence in mediating regulatory T (Treg) cells differentiation, which attach great importance to attenuating acute cellular rejection after liver transplantation (LT). And, miRNAs are known to play essential roles in cell-cell communication delivered by exosomes. However, the function of exosomal miRNAs in regulating Treg cells after LT remains unknown. Here, we performed an expression profiling analysis of exosome-miRNAs from human plasma after LT and investigated their immunoregulatory effects on Treg cells. METHODS: Fifty-eight LT patients and nine donors were included in this report. miRNA profiles in plasma exosomes were analyzed using next-generation sequencing. Flow cytometry, HE and multiplex immunofluorescent staining were used to identify Treg cells in the liver and peripheral blood. A lentiviral vector system was used to overexpress miR-193b-3p in dendritic cells (DCs), and exosomes isolated from these transfected cells were co-cultured with spleen lymphocytesin vitro. A quantitative Real-time PCR and enzyme-linked immunosorbent assay were used to detect the expression of cytokines. RESULTS: Treg cell infiltration was increased in the liver along with Th17 and CD8+ T cell, and it was down-regulated in peripheral blood in the acute rejection group. High-throughput sequencing revealed that miR-193b-3p was markedly up-regulated in plasma exosomes of non-rejection LT patients. The NLRP3 inflammasome was screened as a target for miR-193b-3p based on target prediction and functional enrichment analyses. Exosomal miR-193b-3p derived from DCs increased Treg cells as demonstrated in vitro. miR-193b-3p overexpression down-regulated NLRP3 as well as the inflammatory cytokines IL-1ß and IL-17A while increasing levels of the cytokines IL-10 and TGF-ß. CONCLUSION: DC derived exosomal miR-193b-3p promoted Treg cells by inhibiting NLRP3 expression. These findings not only provide a new perspective on the mechanisms, but also hold great promise for the treatment or prevention of liver allograft rejection.

Domino hepatocyte transplantation using explanted human livers with metabolic defects attenuates D-GalN/LPS-induced acute liver failure.

BACKGROUND: Explanted livers from patients with inherited metabolic liver diseases possess the potential to be a cell source of good-quality hepatocytes for hepatocyte transplantation (HT). This study evaluated the therapeutic effects of domino HT using hepatocytes isolated from explanted human livers for acute liver failure (ALF). METHODS: Isolated hepatocytes were evaluated for viability and function and then transplanted into D-galactosamine/lipopolysaccharide-induced ALF mice via splenic injection. The survival rate was analyzed by the Kaplan-Meier method and log-rank test. Liver function was evaluated by serum biochemical parameters, and inflammatory cytokine levels were measured by ELISA. The pathological changes in the liver tissues were assessed by hematoxylin-eosin staining. Hepatocyte apoptosis was investigated by TUNEL, and hepatocyte apoptosis-related proteins were detected by western blot. The localization of human hepatocytes in the injured mouse livers was detected by immunohistochemical analyses. RESULTS: Hepatocytes were successfully isolated from explanted livers of 10 pediatric patients with various liver-based metabolic disorders, with an average viability of 85.3% ± 13.0% and average yield of 9.2 × 106 ± 3.4 × 106 cells/g. Isolated hepatocytes had an excellent ability to secret albumin, produce urea, uptake indocyanine green, storage glycogen, and express alpha 1 antitrypsin, albumin, cytokeratin 18, and CYP3A4. Domino HT significantly reduced mortality, decreased serum levels of alanine aminotransferase and aspartate aminotransferase, and improved the pathological damage. Moreover, transplanted hepatocytes inhibited interleukin-6 and tumor necrosis factor-α levels. Domino HT also ameliorates hepatocyte apoptosis, as evidenced by decreased TUNEL positive cells. Positive staining for human albumin suggested the localization of human hepatocytes in ALF mice livers. CONCLUSION: Explanted livers from patients with inheritable metabolic disorders can serve as a viable cell source for cell-based therapies. Domino HT using hepatocytes with certain metabolic defects has the potential to be a novel therapeutic strategy for ALF.

ILC2s expanded by exogenous IL-33 regulate CD45+CD11b+F4/80high macrophage polarization to alleviate hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) is an adverse consequence of hepatectomy or liver transplantation. Recently, immune mechanisms involved in hepatic IRI have attracted increased attention of investigators working in this area. In specific, group 2 innate lymphoid cells (ILC2s), have been strongly implicated in mediating type 2 inflammation. However, their immune mechanisms as involved with hepatic IRI remain unclear. Here, we reported that the population of ILC2s is increased with the development of hepatic IRI as shown in a mouse model in initial stage. Moreover, M2 type CD45+CD11b+F4/80high macrophages increased and reached maximal levels at 24 h followed by a significant elevation in IL-4 levels. We injected exogenous IL-33 into the tail vein of mice as a mean to stimulate ILC2s production. This stimulation of ILC2s resulted in a protective effect upon hepatic IRI along with an increase in M2 type CD45+CD11b+F4/80high macrophages. In contrast, depletion of ILC2s as achieved with use of an anti-CD90.2 antibody substantially abolished this protective effect of exogenous IL-33 and M2 type CD45+CD11b+F4/80high macrophage polarization in hepatic IRI. Therefore, this exogenous IL-33 induced potentiation of ILC2s appears to regulate the polarization of CD45+CD11b+F4/80high macrophages to alleviate IRI. Such findings provide the foundation for the development of new targets and strategies in the treatment of hepatic IRI.

Potential correlation of allograft infiltrating group 2 innate lymphoid cells with acute rejection after liver transplantation.

Accumulating evidence indicates the critical roles of group 2 innate lymphoid cells (ILC2s) in immunoregulation. However, the role of ILC2s in acute rejection after liver transplantation (LT) remains elusive. In this study, we analyzed the frequency, counts, and signature cytokines of ILC2s in liver transplant recipients by flow cytometric analysis and multiplex immunofluorescence assay. We also assessed the spatial distribution and correlation between hepatic ILC2s and Treg cells. The changes of ILC2s were dynamically monitored in the mouse LT model. We found that the frequencies of circulating ILC2s were comparable in liver transplant recipients with either rejection or non-rejection compared with the control group. The hepatic ILC2s counts were significantly increased in the rejection group than in the non-rejection and control groups, and a similar trend was observed for Treg cells. In the mouse LT model, allograft infiltrating ILC2s dramatically increased within 14 days post-transplant. The frequency of ILC2s in bone marrow significantly increased at 7 days post-transplant and rapidly decreased at 14 days after LT. Similarly, there was a significant increase in the frequency of splenic ILC2s within two weeks post-transplant. Multiplex immunofluorescence assay showed a close correlation between hepatic ILC2s and Treg cells by analyzing their spatial distribution and distance. In conclusion, the number of allograft infiltrating ILC2s was closely related to rejection after LT. Allograft infiltrating ILC2s may play inhibitory roles in posttransplant immune homeostasis, favoring resolution of liver allograft rejection by interacting with Treg cells or promoting the migration of Tregs cells into the liver allograft.

Characterization and Proteomic Analyses of Proinflammatory Cytokines in a Mouse Model of Liver Transplant Rejection.

Liver transplantation (LT) is an effective strategy for the treatment of end-stage liver disease, but immune rejection remains a significant detriment to the survival and prognosis of these LT patients. While immune rejection is closely related to cytokines, the cytokines investigated within previous studies have been limited and have not included a systematic analysis of proinflammatory cytokines. In the present study, we used a protein chip system and proteomics to detect and analyze serum proinflammatory cytokines and differentially expressed proteins in liver tissue in a mouse model of liver transplantation. In addition, bioinformatics analysis was employed to analyze the proinflammatory cytokines and differential changes in proteins in response to this procedure. With these analyses, we found that serum contents of GC-CSF, CXCL-1, MCP-5, and CXCL-2 were significantly increased after liver transplantation, while IL-5, IL-10, and IL-17 were significantly decreased. Results from Gene Ontology (GO) and KEGG pathway analyses revealed that the cytokine-cytokine receptor, Th1/Th2 cell differentiation, and JAK-STAT signaling pathway were enriched in a network associated with the activation of immune response. Results from our proteomic analysis of liver tissue samples revealed that 470 proteins are increased and 50 decreased, including Anxa1, Anxa2, Acsl4, Sirpa, S100a8, and S100a9. KEGG pathway analysis indicated that the neutrophil extracellular trap formation, NOD-like receptor signaling pathway, and leukocyte transendothelial migration were all associated with liver transplant rejection in these mice. Bioinformatics analysis results demonstrated that CXCL-1/CXCL-2 and S100a8/S100a9 were the genes most closely related to the functions of neutrophils and the mononuclear phagocyte system. These findings provide new insights into some of the critical factors associated with liver transplant rejection and thus offer new targets for the treatment and prevention of this condition.

Characteristics of changes in double positive CD4+CD8+ T cells in liver transplantation.

Although double positive CD4+CD8+ T (DPT) cells has been reported to be involved in some diseases, their trajectory and function as associated with liver transplantation (LT) remain unclear. In the present study, we found that the number of DPT cells was increased in the blood and liver tissue of LT patients. Meanwhile, we compared the distribution of DPT cells in peripheral blood samples and in penetrating liver tissue between liver rejection versus non-rejection patients, as well as the proportion of DPT cells as a function of the extent of liver rejection. The number of DPT cells in the rejection group was significantly increased. An analysis of the spatial distance and correlations between DPT and Treg cells, revealed that these cells showed a high degree of contiguity. In a mouse liver transplant model, the number of DPT cells were significantly increased in liver tissue, and the number of CD8+ T cells gradually increased, while CD4+ T cells decreased as a function of time post-transplantation. Expression level of PD-1 in DPT cells also increased in a temporally-dependent manner post liver transplantation and the changes of PD-1+ DPT cells were related to the degree of liver transplant rejection. In DPT cells interacting with Treg, there was an increased expression of PD-1, which enhanced cellular exhaustion. In conclusion, the capacity for DPT cells to induce immune tolerance may represent a new and important protocol for use in targeting treatments for the prevention of liver transplant rejection.

Clinical evidence of outcomes following liver transplantation in patients with nonalcoholic steatohepatitis: An updated meta-analysis and systematic review.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a dramatically growing indication for liver transplantation (LT) worldwide and the posttransplant outcomes of NASH patients are currently under intensive investigation. This quantitative meta-analysis aimed to update the clinical evidence on outcomes of transplanted patients with NASH. METHODS: We performed a systematic review and meta-analysis of studies (published up to September 15, 2021) that focused on LT outcomes for NASH versus non-NASH patients. Random-effect meta-analysis was conducted to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on crucial baseline clinical characteristics and leave-one-out sensitivity analyses were conducted to assess the robustness of the pooled results. Meta-regression was used to evaluate study-level demographic, clinical, and biochemical characteristics to identify potential confounders affecting patient survival. RESULTS: Twenty-two non-randomized comparative studies with 1,538 NASH and 6,014 non-NASH patients were included. 1- (OR, 0.94; 95% CI, 0.77-1.14), 3- (OR, 0.82; 95% CI, 1.00-1.22), and 5- (OR, 1.05; 95% CI, 0.84-1.31) year patient survival was equivalent between NASH and non-NASH recipients. NASH patients were associated with similar cardiovascular mortality (OR, 1.36; 95% CI, 0.89-2.09) and retransplantation rates (OR, 0.69; 95% CI, 1.03-1.53), lower graft failure-related mortality (OR, 0.11; 95% CI, 0.29-0.74), but higher sepsis-related mortality (OR, 1.53; 95% CI, 1.13-2.06). Meta-regression revealed that a higher proportion of patients with hepatocellular carcinoma (HCC) were associated with significantly superior overall patient survival at 1 (P = 0.044), 3 (P = 0.035) and 5 (P = 0.049) years after LT in NASH compared with non-NASH. CONCLUSIONS: This study shows no difference in posttransplant survival between NASH and non-NASH patients. Carefully selected patients with NASH-related HCC may benefit from LT. NASH recipients should be managed with caution posttransplant, especially regarding the potentially high risk of sepsis-related death.

CD80+ dendritic cell derived exosomes inhibit CD8+ T cells through down-regulating NLRP3 expression after liver transplantation.

BACKGROUND: Graft-infiltrated dendritic cells (DCs) and CD8+ T lymphocytes are closely related with immune regulation after liver transplantation (LT). An additional factor which appears to play an important role with regard to transplantation immunity are exosomes, which are membrane-derived small vesicles released by various cells. However, the regulation of CD80+ DCs derived exosomes on CD8+ T cells in response to LT remains unclear. METHODS: Ten LT patients and two donors were included in this study. Multiple immunofluorescencewas performed to identify infiltratedCD8+ Tcells and DCs in human liver samples. The expression of NLRP3 and Ki-67 were measured usingimmunohistochemistry and immunofluorescence staining.Changes in CD80+ DCs and CD8+ T cells within the liver and blood of a mouse model of LT were detected with flow cytometry. After coculture with CD80+ DCs derived exosomes, the proliferation, adhesion, and transmigration ofCD8+ T cells were determined with the use of CCK-8, Adhesion and Transmigration assay in vitro.CD8+ T cells related cytokines were measured using Western blot, qRT-PCR and ELISA. RESULTS: In human liver samples, there was an increase in intrahepatic CD8+ T cell infiltration in the acute LT rejection group, an effect which was accompanied by high expressions of NLRP3 and Ki-67 index and a decrease in DCs. Similarly, lower levels of CD80+ DCs were observed with acute rejection in an LT mouse model, along with increased numbers of CD8+ T cells in the liver and blood. In vitro, CD80+ DCs derived exosomes modulated the secretion of CD8+ T cells from cytokines by down-regulating NLRP3 expression, combined with a synchronous inhibition in the adhesion, invasion, and proliferation of CD8+ T cells. CONCLUSION: CD80+ DCs derived exosomes negatively regulate CD8+ T cells via inhibition of NLRP3 expression, a series of events which are essential to attenuate acute LT rejection. These results reveal a new role for CD80+ DCs exosomes as related to tolerance induction in LT.

Therapeutic potential of living donor liver transplantation from heterozygous carrier donors in children with propionic acidemia.

BACKGROUND: Current world experience regarding living donor liver transplantation (LDLT) in the treatment of propionic acidemia (PA) is limited, especially in terms of using obligate heterozygous carriers as donors. This study aimed to evaluate the clinical outcomes of LDLT in children with PA. METHODS: From November 2017 to January 2020, 7 of the 192 children who underwent LDLT at our institution had been diagnosed with PA (median age, 2.1 years; range, 1.1-5.8 years). The primary indication for transplantation was frequent metabolic decompensations in 6 patients and preventative treatment in 1 patient. Of the seven parental living donors, six were genetically proven obligate heterozygous carriers. RESULTS: During a median follow-up of 23.9 months (range, 13.9-40.2 months), all patients were alive with 100% allograft survival, and no severe transplant-related complications occurred. In the case of liberalized protein intake, they did not suffer metabolic decompensation or disease-related complications and made progress in neurodevelopmental delay and body growth, as well as blood and urinary metabolite levels. In one patient with pre-existing mild dilated cardiomyopathy, her echocardiogram results completely normalized 13.8 months post-transplant. All living donors recovered well after surgery, with no metabolic decompensations or procedure-related complications. Western blotting revealed that the hepatic expressions of PCCA and PCCB in one of the heterozygous donors were comparable to those of the normal healthy control at the protein level. CONCLUSIONS: LDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected PA patients, with no negative impact on donors' and recipients' clinical courses.